[Recommendations for Primary Health Care for transgender people]. / Recomendaciones para la atención de la salud en Atención Primaria de las personas transgénero.

The WHO defines Primary Health Care as essential health care, based on practical, scientifically founded and socially acceptable methods and technologies, made available to all individuals and families in the community, through their full participation, and at a cost that the community and the country can bear, at each and every stage of their development, in a spirit of self-responsibility and self-determination. With the intention of fulfilling the basic objective of caring for and promoting health in all the groups that make up our current society, the need arises to focus on certain groups in which the actions of Primary Care are currently consensual or poorly protocolised, as is the case with the health care of transgender people.

Valorization of steelmaking slag and coal fly ash as amendments in combination with Betula pubescens for the remediation of a highly As- and Hg-polluted mining soil.

Soil pollution by As and Hg is a pressing environmental issue given their persistence. The intricate removal processes and subsequent accumulation of these elements in soil adversely impact plant growth and pose risks to other organisms in the food chain and to underground aquifers. Here we assessed the effectiveness of non-toxic industrial byproducts, namely coal fly ash and steelmaking slag, as soil amendments, both independently and in conjunction with an organic fertilizer. This approach was coupled with a phytoremediation technique involving Betula pubescens to tackle soil highly contaminated. Greenhouse experiments were conducted to evaluate amendments' impact on the growth, physiology, and biochemistry of the plant. Additionally, a permeable barrier made of byproducts was placed beneath the soil to treat leachates. The application of the byproducts reduced pollutant availability, the production of contaminated leachates, and pollutant accumulation in plants, thereby promoting plant development and survival. Conversely, the addition of the fertilizer alone led to an increase in As accumulation in plants and induced the production of antioxidant compounds such as carotenoids and free proline. Notably, all amendments led to increased thiolic compound production without affecting chlorophyll synthesis. While fertilizer application significantly decreased parameters associated with oxidative stress, such as hydrogen peroxide and malondialdehyde, no substantial reduction was observed after byproduct application. Thermal desorption analysis of the byproducts revealed Hg immobilization mechanisms, thereby indicating retention of this metalloid in the form of Hg chloride. In summary, the revalorization of industrial byproducts in the context of the circular economy holds promise for effectively immobilizing metal(loid)s in heavily polluted soils. Additionally, this approach can be enhanced through synergies with phytoremediation.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia and normal perfusion.

BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (p<0.001), and stress (p=0.003), SI end-systolic rest (p=0.002) and stress (p<0.001) as well as statistically significant lower values of EI rest (p<0.001) and stress (p<0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (p<0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (p<0.05). CONCLUSIONS: Shape and eccentricity indexe s differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

Dualismo, modulación alostérica y señalización diferencial en los receptores opiáceos: futuro potencial terapéutico / Dualism, allosteric modulation and biased signaling of opioid receptors: Future therapeutic potential

Los fármacos opioides permanecen como fármacos de elección en el tratamiento del dolor agudo postoperatorio y del dolor crónico oncológico. Su prescripción inadecuada, ha dado lugar, en algunos países, a una verdadera «crisis de opioides». En este contexto, puede resultar interesante el potencial terapéutico de algunos ligandos que actúan como moduladores alostéricos de la fijación de los agonistas opioides y su capacidad de modular su actividad, modificando su afinidad, potencia e incluso eficacia. (AU)

Opioids are still the drugs of choice for the treatment of acute post-surgical pain and chronic cancer pain. Overprescribing of these drugs has given rise to an “opioid crisis” in some countries. In this context, attention has been drawn to the therapeutic potential of various ligands that act as allosteric modulators of orthosteric binding sites and modulate the drug's activity, affinity, potency, and even efficacy. (AU)

Immune-mediated hepatitis: Basic concepts and treatment.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.

Comparison of metagenomic and traditional methods for diagnosis of E. coli enteric infections.

Diarrheagenic Escherichia coli, collectively known as DEC, is a leading cause of diarrhea, particularly in children in low- and middle-income countries. Diagnosing infections caused by different DEC pathotypes traditionally relies on the cultivation and identification of virulence genes, a resource-intensive and error-prone process. Here, we compared culture-based DEC identification with shotgun metagenomic sequencing of whole stool using 35 randomly drawn samples from a cohort of diarrhea-afflicted patients. Metagenomic sequencing detected the cultured isolates in 97% of samples, revealing, overall, reliable detection by this approach. Genome binning yielded high-quality E. coli metagenome-assembled genomes (MAGs) for 13 samples, and we observed that the MAG did not carry the diagnostic DEC virulence genes of the corresponding isolate in 60% of these samples. Specifically, two distinct scenarios were observed: diffusely adherent E. coli (DAEC) isolates without corresponding DAEC MAGs appeared to be relatively rare members of the microbiome, which was further corroborated by quantitative PCR (qPCR), and thus unlikely to represent the etiological agent in 3 of the 13 samples (~23%). In contrast, ETEC virulence genes were located on plasmids and largely escaped binning in associated MAGs despite being prevalent in the sample (5/13 samples or ~38%), revealing limitations of the metagenomic approach. These results provide important insights for diagnosing DEC infections and demonstrate how metagenomic methods can complement isolation efforts and PCR for pathogen identification and population abundance. IMPORTANCE: Diagnosing enteric infections based on traditional methods involving isolation and PCR can be erroneous due to isolation and other biases, e.g., the most abundant pathogen may not be recovered on isolation media. By employing shotgun metagenomics together with traditional methods on the same stool samples, we show that mixed infections caused by multiple pathogens are much more frequent than traditional methods indicate in the case of acute diarrhea. Further, in at least 8.5% of the total samples examined, the metagenomic approach reliably identified a different pathogen than the traditional approach. Therefore, our results provide a methodology to complement existing methods for enteric infection diagnostics with cutting-edge, culture-independent metagenomic techniques, and highlight the strengths and limitations of each approach.

[Antibiotic stewardship programs in the Spanish emergency services: PROA-URG Study]. / Programas de optimización del uso de antimicrobianos en los servicios de urgencias españoles: Estudio PROA-URG.

OBJECTIVE: Antimicrobial stewardship programs (ASP) have become a key tool in the adaptation of these drugs to the health system. The information available on the application and indicators used in these programs in emergency departments is scarce. The objective of this study is to know the extent of ASP implementation in the emergency departments, as well as the use of antimicrobials in these units. METHODS: Multicenter retrospective study. An invitation was sent to all participants of the REDFASTER-SEFH emergency pharmacist working group. A questionnaire was used consisting of 21 items, answered by a team made up of a pharmacist, emergency room specialist, infectious disease specialist and microbiologist. RESULTS: Eighteen hospitals completed the survey. Fourteen (77.8%) had an ASP manager. The DDD value per 1000 admissions ranged between 36.5 and 400.5 (median: 100.4 [IQR:57.2-157.3]). Both carbapenem and macrolide group presented wide variability in use. Six (33.3%) hospitals had an annual report on the specific resistance profile for urine and blood cultures. The percentage of multi-drug resistant strains in urine cultures was 12.5% and in blood cultures 12.2%. The percentage of adequacy in the bacteremia treatment was 81.0% (IQR:74.6-85.0%), while in urinary tract infections was 78.0% (IQR:71.5-88.0). CONCLUSIONS: Despite the existence of ASP members in emergency services, as well as the training activity and local guidelines is common. knowledge of the use of antimicrobials and resistances is limited. Future activities must be aimed at improving information about the ASP results in these units.

Does elite European match-play affect salivary immunoglobulin-A and cortisol in soccer players? The influence of playing status and match outcome.

Introduction: The aims of this study were to: a) investigate salivary immunoglobulin A (s-IgA) and cortisol (s-Cort) responses to nine competitive fixtures in starting and non- starting soccer players; and b) compare s-IgA and s-Cort responses of starters and non-starters considering match outcome. Methods: Saliva from 19 male outfield players from an elite soccer team (mean ± SD, age 26 ± 4 years; weight 80.5 ± 8.1 kg; height 1.83 ± 0.07 m; body-fat 10.8% ± 0.7%) was collected. Saliva samples were taken on the day before each match (MD-1), 60-min before kick-off (MDpre), 30-min post-match (MDpost), and 72-h post-match (MD+3). There were five wins, one draw and three losses. Results: The mean s-IgA value was found to be significantly lower at MD+3 compared to MDpre and MDpost. s-Cort was significantly higher at MDpost compared to MD-1 and MDpre. When compared to MDpre, a statistically significant decrease in s-Cort was observed at MD+3 compared to MDpost. Starters displayed higher s-Cort values across the nine matches. There was a significant group-by-time interaction for s-Cort. There was a significant increase in s-Cort levels at MDpost compared to MD-1 and from MDpre to MDpost in starting players. At MDpost, starters had significantly higher s-Cort values. s-IgA values of starting and non- starting players following successful and unsuccessful matches did not reveal a significant difference. However, similar analysis of s-Cort in successful matches showed a significant difference between starters and non-starters. s-IgA values at MD-1, MDpre, MDpost and MD+3 in starters and non-starters following successful and unsuccessful matches revealed significant differences at MDpre and MDpost in starters, respectively. Furthermore, s-Cort values at MD-1, MDpre, MDpost and MD+3 in starters and non-starters in successful and unsuccessful matches revealed significant differences at MD+3 in starting players. Discussion: The present study suggests that in elite level soccer players, both starting status and match outcome influence s-IgA and s-Cort responses, particularly starters. Specifically, s-IgA was lower for starters before and after the match following successful outcomes. Moreover, higher s-Cort values were found before the match while lower values occurred after the match for starters in successful matches.

Influence of lymphopenia on long-term mortality in septic shock, a retrospective observational study.

BACKGROUND AND OBJECTIVE: The diagnosis of infection, to diagnose septic shock, has been qualified by leukocyte counts and protein biomarkers. Septic shock mortality is persistently high (20%-50%), and rising in the long term. The definition of sepsis does not include leukocyte count, and lymphopenia has been associated with its mortality in the short term. Immunosuppression and increased mortality in the long term due to sepsis have not been demonstrated. The aim is to relate the occurrence of lymphopenia and its lack of recovery during septic shock with mortality at 2 years. PATIENTS AND METHODS: Cohort of 332 elderly patients diagnosed with septic shock. Mortality at 28 days and 2 years was analysed according to leukocyte, neutrophil, and lymphocyte counts, and the ability to recover from lymphopenia (LRec). RESULTS: A total of 74.1% of patients showed lymphopenia, and 73.5% did not improve during ICU stay. Mortality was 31.0% and 50.3% at 28 days and 2 years, respectively. Lymphopenia was a predictor of early mortality (OR 2.96) and LRec of late mortality (OR 3.98). Long-term mortality was associated with LRec (HR 1.69). CONCLUSIONS: In elderly patients with septic shock, 28-day mortality is associated with lymphopenia and neutrophilia, and LRec with 2-year mortality; this may represent 2 distinct phenotypes of behaviour after septic shock.

Achievements and challenges in the health of Mexican women, 1990 and 2019: ecological analysis based on the global burden of disease data.

OBJECTIVES: To describe the burden and causes of disease in Mexican women in 1990 and 2019, based on the data disaggregation by age groups and states. Also, to evaluate the relationship of years of healthy life lost with the Socio-demographic Index (SDI) and with the Healthcare Access and Quality (HAQ) Index. STUDY DESIGN: This was an ecological descriptive study. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study study, the age-standardized and age-specific rates for mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were reported. RESULTS: At the national level, the all-cause age-standardized rates for Mexican women decreased in mortality -28.8%; YLLs -39.8%; YLDs -1.3%; and DALYs -26.2%. For 2019, the indicators analyzed had the worst performances in Chiapas and Chihuahua, while women in Sinaloa had the lowest age-standardized rates. In 1990, it is worth noting that there was a remarkable presence of CDs, mainly in YLLs. In all age groups, diabetes mellitus was the leading cause of DALYs in Mexico's 32 states, followed by CKD (in 24 states), and ischemic heart disease (in 18 states). In both 1990 and 2019, a negative and statistically significant correlation between DALYs and the HAQ Index was evident. The correlation between DALYs and the SDI was only significant in 1990. CONCLUSION: In the last 30 years, the burden of disease on Mexican women has undergone substantial changes that reflect progress in the improvement of their health conditions. However, the current scenario is complex because the convergence of communicable diseases, non-communicable diseases, and injuries is evident, which implies important challenges that must be addressed as soon as possible.

The non-vesicle cell-free DNA (cfDNA) induces cell transformation associated with horizontal DNA transfer.

BACKGROUND: Cell-free DNA (cfDNA) is a source for liquid biopsy used for cancer diagnosis, therapy selection, and disease monitoring due to its non-invasive nature and ease of extraction. However, cfDNA also participates in cancer development and progression by horizontal transfer. In humans, cfDNA circulates complexed with extracellular vesicles (EV) and macromolecular complexes such as nucleosomes, lipids, and serum proteins. The present study aimed to demonstrate whether cfDNA not associated with EV induces cell transformation and tumorigenesis. METHODS: Supernatant of the SW480 human colon cancer cell line was processed by ultracentrifugation to obtain a soluble fraction (SF) and a fraction associated with EV (EVF). Primary murine embryonic fibroblast cells (NIH3T3) underwent passive transfection with these fractions, and cell proliferation, cell cycle, apoptosis, cell transformation, and tumorigenic assays were performed. Next, cfDNA was analyzed by electronic microscopy, and horizontal transfer was assessed by human mutant KRAS in recipient cells via PCR and recipient cell internalization via fluorescence microscopy. RESULTS: The results showed that the SF but not the EVF of cfDNA induced proliferative and antiapoptotic effects, cell transformation, and tumorigenesis in nude mice, which were reduced by digestion with DNAse I and proteinase K. These effects were associated with horizontal DNA transfer and cfDNA internalization into recipient cells. CONCLUSIONS: The results suggest pro-tumorigenic effects of cfDNA in the SF that can be offset by enzyme treatment. Further exploration of the horizontal tumor progression phenomenon mediated by cfDNA is needed to determine whether its manipulation may play a role in cancer therapy.

First measurements of an imaging heavy ion beam probe at the ASDEX Upgrade tokamak.

The imaging heavy ion beam probe (i-HIBP) diagnostic has been successfully commissioned at ASDEX Upgrade. The i-HIBP injects a primary neutral beam into the plasma, where it is ionized, leading to a fan of secondary (charged) beams. These are deflected by the magnetic field of the tokamak and collected by a scintillator detector, generating a strike-line light pattern that encodes information on the density, electrostatic potential, and magnetic field of the plasma edge. The first measurements have been made, demonstrating the proof-of-principle of this diagnostic technique. A primary beam of 85/87Rb has been used with energies ranging between 60 and 72 keV and extracted currents up to 1.5 mA. The first signals have been obtained in experiments covering a wide range of parameter spaces, with plasma currents (Ip) between 0.2 and 0.8 MA and on-axis toroidal magnetic field (Bt) between 1.9 and 2.7 T. Low densities appear to be critical for the performance of the diagnostic, as signals are typically observed only when the line integrated density is below 2.0-3.0 × 1019 m-2 in the central interferometer chord, depending on the plasma shape. The strike line moves as expected when Ip is ramped, indicating that current measurements are possible. Additionally, clear dynamics in the intensity of the strike line are often observed, which might be linked to changes in the edge profile structure. However, the signal-to-background ratio of the signals is hampered by stray light, and the image guide degradation is due to neutron irradiation. Finally, simulations have been carried out to investigate the sensitivity of the expected signals to plasma density and temperature. The results are in qualitative agreement with the experimental observations, suggesting that the diagnostic is almost insensitive to fluctuations in the temperature profile, while the signal level is highly determined by the density profile due to the beam attenuation.

Controversies in point-of-care 3D printing for oncological and reconstructive surgery with free software in oral and maxillofacial surgery: European regulations, costs, and timeframe.

The aim of this paper is to discuss the controversies surrounding the most recent European regulations, as well as the cost, for a 3D printing workflow using free-source software in the context of a tertiary level university hospital in the Spanish public health system. Computer-aided design and manufacturing (CAD/CAM) for head and neck oncological surgery with the printing of biomodels, cutting guides, and patient-specific implants has made it possible to simplify and make this type of highly complex surgery more predictable. This technology is not without drawbacks, such as increased costs and the lead times when planning with the biomedical industry. A review of the current European legislation and the literature on this subject was performed, and comparisons made with the authors' in-house 3D printing setup using free software and different 3D printers. The cost analysis revealed that for the cheapest setup with free software, it would be possible to amortize the investment from case 2, and in all cases the initial investment would be amortized before case 9. The timeframe ranged from 2 weeks with the biomedical industry to 72 h with point-of-care 3D printing. It is now possible to develop point-of-care 3D printing in any hospital with almost any budget.

Pork carcass composition, meat and belly qualities as influenced by feed efficiency selection in replacement boars from Large White sire and dam lines.

This study evaluated carcass attributes, meat and belly qualities in finisher boars (n = 79) selected for feed efficiency (low, intermediate and high) based on estimated breeding value for feed conversion ratio within a Large White dam and sire genetic lines. The sire line had lower trimmed fat proportions and higher lean than the dam line (P < 0.01). Genetic lines expressed slight colour changes and drip losses (P < 0.05), with no differences in pH, marbling and cooking traits (P > 0.05). High-efficient animals presented the highest lean yield (P < 0.01), the lowest trimmed fat proportion (P < 0.01) and no effect on meat and belly quality attributes (P > 0.05) compared with other efficient groups. Interaction between efficiency group and genetic line was only detected for belly weight and thickness (P < 0.01). High-efficient animals offer a greater leanness level, with minimal impact on meat and belly quality traits.

Plasma and milk metabolomics revealed changes in amino acid metabolism in Holstein dairy cows under heat stress.

Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D3/Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe-, n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+, n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI: 72.0-82.0) supplemented with different levels of vitamin D3/Ca: either low (HS/DCa-, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0-64.0) receiving the low dose of vitamin D3/Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe-/DCa-, and (2) the vitamin E/Se and vitamin D3/Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P < 0.01) on day 14, and taurine was decreased (-65%, P < 0.01) on day 14 in the heat stress (HS) cows, compared with day 0. Most compounds were unaffected by vitamin E/Se or vitamin D3/Ca supplementation level or their interaction (FDR > 0.05) in plasma and milk, except for milk alanine which was lower (-69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se-. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D3/Ca or their combination did not appear to affect the metabolic remodeling triggered by HS.

"They Protect us as if they were our Mom" Masking Attitudes from Freelist Survey Data and Qualitative Interviews in San Diego School Communities.

BACKGROUND: Despite being disproportionately impacted by COVID-19 due to a lack of structural support, marginalized communities have been largely ignored in the politically polarized debate over school masking. In response to this, we sought to explore masking attitudes by centering the voices of parents and children at historically marginalized, predominantly Hispanic schools in southern California. METHODS: We conducted a mixed-methods study with parents and children attending 26 low-income predominantly Hispanic-serving elementary schools. A random sample of parents was asked to provide a freelist of words they associate with masking. A subset of parents with children aged 4-6 was recruited from these surveys to participate in parent-child interviews (PCI). We calculated Smith's salience index for all unique items, stratifying by language (English/Spanish). Item salience guided PCI thematic analysis for additional context and meaning. RESULTS: 648 participants provided 1118 unique freelist items in English and Spanish. 19 parent-child pairs were interviewed, 11 in Spanish and 8 in English. The most salient words were "safety"(0.37), "protection"(0.12), "prevention"(0.05), "health"(0.04), "good"(0.03), "can't breathe"(0.03), "necessary"(0.02), "care"(0.02), "precaution"(0.02), and "unnecessary"(0.02). Spanish speakers had a more favorable view of masking than English speakers, particularly regarding "protection" (0.20 vs 0.08) and "prevention" (0.10 vs 0.02). DISCUSSION: Masking is an affordable individual-level risk mitigation that protects the communities that have inequitably shouldered the burdens of the COVID-19 pandemic. We recommend that policymakers prioritize the views of those most impacted when deciding on risk mitigation policies like school masking.